Macromolecular antioxidants based on sterically hindered phenols and phosphites

ABSTRACT

A sterically hindered phenol and phosphite based compound represented by the following formula: 
     
       
         
         
             
             
         
       
         
         
           
             and its use as an antioxidant in a wide range of materials including, but not limited to, food, plastics, elastomers, composites and petroleum based products is disclosed herein.

RELATED APPLICATIONS

This application is a continuation of U.S. application Ser. No.13/109,800, filed May 17, 2011 now U.S. Pat. No. 8,242,230, which is adivisional of U.S. application Ser. No. 12/789,843, filed May 28, 2010now U.S. Pat. No. 7,956,153, which is a continuation of U.S. applicationSer. No. 11/293,844, filed Dec. 2, 2005 now U.S. Pat. No. 7,902,317,which claims the benefit of U.S. Provisional Application No. 60/633,196,filed on Dec. 3, 2004. The entire teachings of the above applicationsare incorporated herein by reference.

BACKGROUND OF THE INVENTION

Antioxidants are employed to prevent oxidation in a wide range ofmaterials, for example, plastics, elastomers, lubricants, petroleumbased products (lubricants, gasoline, aviation fuels, and engine oils),cooking oil, cosmetics, processed food products, and the like. Whilemany small molecule antioxidants exist, there is a continuing need fornew antioxidants that have improved properties.

The commercial use of triaryl phophites in latex is well known. Triarylphophites containing alkyl-substituted phenyl rings have been found tobe effective synthetic latex stabilizers. However, there is a continuingneed for antioxidants with higher antioxidant activity and higherthermal stability.

SUMMARY OF THE INVENTION

The present invention relates to high performance, sterically hindered,phenol and phosphite based macromolecular antioxidants. In certainembodiments, the sterically hindered, phenol and phosphite basedmacromolecules of the present invention have enhanced antioxidantactivity and better thermal stability compared to commercially availableantioxidants.

In particular, the present invention pertains to sterically hinderedphenol and phosphite based compounds represented by a formula selectedfrom I-III:

R is:

R₁ and R₂ in each occurrence, independently is an optionally substitutedalkyl, an optionally substituted aryl or an optionally substitutedaralkyl.

X and Y in each occurrence, independently is a bond, —O—, —NH—,—C(O)NH—, —NHC(O)—, —C(O)O—, —OC(O)— or —CH₂—.

n and m in each occurrence, is independently 0 or a positive integer.

i and j in each occurrence, independently is 0, 1, 2, 3 or 4.

R″ is an optionally substituted alkyl.

In another embodiment, the present invention pertains to methods ofpreventing oxidation. The method comprises combining an oxidizablematerial with a compound represented by a structural formula selectedfrom I-III.

In yet another embodiment, the present invention pertains to methods forpreparing sterically hindered phenol and phosphite based compound,having a formula selected from I-III. The method comprises combining aphenol containing compound with a phosphorous containing compound, suchas, phosphorous trichloride in a suitable solvent under conditionssuitable for reaction of the phenol containing compound with thephosphorous containing compound.

In yet another embodiment the present invention pertains to the use ofthe disclosed compounds as antioxidants in a wide range of materialsincluding, but not limited to, food, plastics, elastomers, compositesand petroleum based products.

The compounds of the invention provide significant oxidative resistanceand thermal stability. The compounds of the invention generally havehigher oxidative induction time, higher thermal stability and lowerchange of Melt flow or viscosity than commercially availableantioxidants Without wishing to be bound by theory it is believed thatthe enhanced molecular activity comes from the synergistic chemistrybetween the two main integral components (phenolic and phosphitecomponents) of these macromolecular antioxidants.

In certain embodiments, the compounds disclosed herein, do not discolorthe substance to which they are added. In certain other embodiments thecompounds disclosed herein impart fewer odors to the substance to whichthey are added than currently available antioxidants. In certain otherembodiments, the disclosed compounds provide enhanced oven agingproperties to organic materials subject to attack by heat and oxygen. Incertain other embodiments the disclosed compounds have higherantioxidant activity and higher thermal stability than antioxidantswhich are currently known or used in the art.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1, is a comparison of the Oxidative Induction Time (OIT) of oneembodiment of the invention, namely,tris[N-(4-hydroxyphenyl),-3-(2,6-di-tert.-butyl,4-hydroxyphenyl)propionamide]phosphate, versus commercially availableIrganox®1010 in polypropylene (PP) at 1000 ppm (extruded at 230° C.).

FIG. 2 is the Fourier Transform Infrared (FT-IR) spectrum oftris[N-(4-hydroxyphenyl),-3-(2,6-di-tert.-butyl,4-hydroxyphenyl)propionamide]phosphate of the invention.

FIG. 3 is the Ultraviolet (UV) spectrum oftris[N-(4-hydroxyphenyl),-3-(2,6-di-tert.-butyl, 4-hydroxyphenyl)propionamide]phosphate of the invention.

FIG. 4 is the Thermogravimetric Analysis (TGA) oftris[N-(4-hydroxyphenyl),-3-(2,6-di-tert.-butyl,4-hydroxyphenyl)propionamide]phosphate of the invention, obtained usinga 2950 TGA HR V5 4A and a Universal V3.88 TA with a sample size of7.7400 mg by a Ramp method.

DETAILED DESCRIPTION OF THE INVENTION

The foregoing and other objects, features and advantages of theinvention will be apparent from the following more particulardescription of preferred embodiments of the invention, as illustrated inthe accompanying drawings in which like reference characters refer tothe same parts throughout the different views. The drawings are notnecessarily to scale, emphasis instead being placed upon illustratingthe principles of the invention.

In one embodiment, the present invention pertains to sterically hinderedphenol and phosphite based compounds, represented by a formula selectedfrom I-III:

R is:

R₁ and R₂ in each occurrence, independently is an optionally substitutedalkyl, optionally substituted aryl or optionally substituted aralkyl. Inone embodiment, each R₁ and R₂ are independently an optionallysubstituted alkyl. In another embodiment, each R₁ and R₂ areindependently a C1-C6 alkyl.

In one embodiment R is:

In another embodiment R is:

In yet another embodiment R is:

X and Y in each occurrence independently is a bond, —O—, —NH—, —C(O)NH—,—NHC(O)—, —C(O)O—, —OC(O)— or —CH₂—. In one embodiment, X and Y in eachoccurrence independently is a bond or —CH₂—. In another embodiment. Xand Y in each occurrence independently is a bond, —O— or —CH₂—. In yetanother embodiment, X and Y in each occurrence independently is a bond,—NH— or —CH₂—. In yet another embodiment, X and Y in each occurrenceindependently is a bond, —C(O)NH— or —CH₂—. In yet another embodiment, Xand Y in each occurrence independently is a bond, —NHC(O)—, or —CH₂—. Inyet another embodiment, X and Y in each occurrence independently is abond, —C(O)O— or —CH₂—. In yet another embodiment, X and Y in eachoccurrence independently is a bond, —OC(O)— or —CH₂—.

n and m in each occurrence independently is 0 or a positive integer. Inone embodiment, n and m in each occurrence independently is 0 to 18. Inanother embodiment, n and m in each occurrence independently is 0 to 12.In yet another embodiment, n and m are in each occurrence independentlyis 0 to 6.

i and j in each occurrence independently is 0, 1, 2, 3 or 4. In oneembodiment i and j in each occurrence independently is 0, 1 or 2. In aparticular embodiment, i is 0. In another particular embodiment j is 2.

R″ is an optionally substituted alkyl. In one embodiment R″ is C1-C6alkyl.

In one embodiment the present invention pertains to compoundsrepresented by structural formula I.

In one embodiment the present invention pertains to compoundsrepresented by structural formula II.

In one embodiment the present invention pertains to compoundsrepresented by structural formula III.

In a particular embodiment, for compounds of the present inventionrepresented by structural formulas I-III, R is:

and n and m in each occurrence independently is 0 to 12, and theremainder of the variables are as described above for structuralformulas I-III.

In another particular embodiment, for compounds of the present inventionrepresented by structural formulas I-III, R, n and m are as describedimmediately above, and R₁ and R₂ in each occurrence, independently is anoptionally substituted alkyl; i and j in each occurrence independentlyis 0, 1 or 2; and the remainder of the variables are as described abovefor structural formulas I-III.

In yet another particular embodiment, for compounds of the presentinvention represented by structural formulas I-III, R₁, R₂, i and j areas described immediately above, and R is:

n and m in each occurrence, independently is 0 to 6; and the remainderof the variables are as described above for structural formulas I-III.

In another particular embodiment, for compounds of the present inventionrepresented by structural formulas I-III, R₁, R₂, i, j, R, n and m areas described immediately above, and X and Y in each occurrence,independently is a bond or —CH₂—; and the remainder of the variables areas described above for structural formulas I-III.

In another particular embodiment, for compounds of the present inventionrepresented by structural formulas I-III R₁, R₂, i, j, R, n and m are asdescribed immediately above, and X and Y in each occurrence,independently is a bond, —O— or —CH₂—; and the remainder of thevariables are as described above for structural formulas I-III.

In another particular embodiment, for compounds of the present inventionrepresented by structural formulas I-III, R₁, R₂, i, j, R, n and m areas described immediately above, and X and Y in each occurrence,independently is a bond, —NH— or —CH₂—; and the remainder of thevariables are as described above for structural formulas I-III.

In another particular embodiment, for compounds of the present inventionrepresented by structural formulas I-III, R₁, R₂, i, j, R, n and m areas described immediately above, and X and Y in each occurrence,independently is a bond, —C(O)NH— or —CH₂—; and the remainder of thevariables are as described above for structural formulas I-III.

In another particular embodiment, for compounds of the present inventionrepresented by structural formulas I-III, R₁, R₂, i, j, R, n and m areas described immediately above, and X and Y in each occurrence,independently is a bond, —NHC(O)—, or —CH₂—; and the remainder of thevariables are as described above for structural formulas I-III.

In another particular embodiment, for compounds of the present inventionrepresented by structural formulas I-III, R₁, R₂, i, j, R, n and m areas described immediately above, and X and Y in each occurrence,independently is a bond, —C(O)O— or —CH₂—; and the remainder of thevariables are as described above for structural formulas I-III.

In another particular embodiment, for compounds of the present inventionrepresented by structural formulas I-III, R₁, R₂, i, j, R, n and m areas described immediately above, and X and Y in each occurrence,independently is a bond, —OC(O)— or —CH₂—; and the remainder of thevariables are as described above for structural formulas I-III.

In an additional embodiment, for formulas I-III R is:

n and m in each occurrence, independently is 0 or a positive integer. Inone embodiment, n and m in each occurrence, independently is 0 to 18. Inanother embodiment, n and m in each occurrence, independently is 0 to12. In yet another embodiment, n and m in each occurrence, independentlyis 0 to 6.

i and j in each occurrence, independently is 0, 1, 2, 3 or 4. In oneembodiment, i and j in each occurrence, independently is 0, 1 or 2. In aparticular embodiment, i is 0. In another particular embodiment, j is 2.

Z′ is —C(O)O—, —OC(O)—, —C(O)NH—, —NHC(O)—, —NH—, —CH═N—, —C(O)—, —O—,—S—, —C(O)OC(O)— or a bond. In one embodiment, Z′ is —C(O)O—. In anotherembodiment, Z′ is —OC(O)—. In yet another embodiment, Z′ is —C(O)NH—. Inyet another embodiment, Z′ is —NHC(O)—. In yet another embodiment, Z′ is—NH—. In yet another embodiment, Z′ is —CH═N—. In yet anotherembodiment, Z′ is —C(O)—. In yet another embodiment, Z′ is —O—. In yetanother embodiment, Z′ is —S—. In yet another embodiment, Z′ is—C(O)OC(O)—. In yet another embodiment, Z′ is a bond.

R′ is an optionally substituted C1-C6 alkyl, —OH, —NH₂, —SH, anoptionally substituted aryl, an ester or

wherein at least one R′ adjacent to the —OH group is an optionallysubstituted bulky alkyl group (e.g., butyl, sec-butyl, tert-butyl,2-propyl, 1,1-dimethylhexyl, and the like).

R′₁ is an optionally substituted C1-C6 alkyl, an optionally substitutedaryl, an optionally substituted aralkyl, —OH, —NH₂, —SH, or C1-C6 alkylester wherein at least one R₁ adjacent to the —OH group is a bulky alkylgroup (e.g., butyl, sec-butyl, tert-butyl, 2-propyl, 1,1-dimethylhexyl,and the like).).

R′₂ is an optionally substituted C1-C6 alkyl, an optionally substitutedaryl, an optionally substituted aralkyl, —OH, —NH₂, —SH, or ester.

X′ is —C(O)O—, —OC(O)—, —C(O)NH—, —NHC(O)—, —NH—, —CH═N—, —C(O)—, —O—,—S—, —C(O)OC(O)— or a bond. In one embodiment X′ is —C(O)O—. In anotherembodiment X′ is —OC(O)—. In yet another embodiment X′ is —C(O)NH—. Inyet another embodiment X′ is —NHC(O)—. In yet another embodiment X′ is—NH—. In yet another embodiment X′ is —CH═N—. In yet another embodimentX′ is —C(O)—. In yet another embodiment X′ is —O—. In yet anotherembodiment X′ is —S—. In yet another embodiment X′ is —C(O)OC(O)—. Inyet another embodiment X′ is a bond.

M′ is H, an optionally substituted aryl, an optionally substitutedC1-C20 linear or branched alkyl chain with or without any functionalgroup anywhere in the chain, or

o is 0 or a positive integer. Preferably o is 0 to 18. More preferably ois 0 to 12. Even more preferably o is 0 to 6.

In yet another embodiment, for formulas I-III R is:

R′₂ is C1-C6 alkyl, —OH, —NH₂, —SH, aryl, ester, aralkyl or

wherein at least one R′₂ is —OH, and the values and preferred values forthe remainder of the variables for R are as described immediately above.

In yet another embodiment, the present invention relates to a compoundof formula I-III, wherein M is

Wherein p is 0, 1, 2, 3 or 4; and the values and preferred values forthe remainder of the variables are as described above for formulasI-III.

The term “alkyl” as used herein means a saturated straight-chain,branched or cyclic hydrocarbon. When straight-chained or branched, analkyl group is typically C1-C8, more typically C1-C6; when cyclic, analkyl group is typically C3-C12, more typically C3-C7 alkyl ester.Examples of alkyl groups include methyl, ethyl, n-propyl, iso-propyl,n-butyl, sec-butyl and tert-butyl and 1,1-dimethylhexyl.

The term “alkoxy” as used herein is represented by —OR**, wherein R** isan alkyl group as defined above.

The term “acyl” as used herein is represented by —C(O)R**, wherein R**is an alkyl group as defined above.

The term “alkyl ester” as used herein means a group represented by—C(O)OR**, where R** is an alkyl group as defined above.

The term “aromatic group” used alone or as part of a larger moiety as in“aralkyl”, includes carbocyclic aromatic rings and heteroaryl rings. Theterm “aromatic group” may be used interchangeably with the terms “aryl”,“aryl ring” “aromatic ring”, “aryl group” and “aromatic group”.

Carbocyclic aromatic ring groups have only carbon ring atoms (typicallysix to fourteen) and include monocyclic aromatic rings such as phenyland fused polycyclic aromatic ring systems in which two or morecarbocyclic aromatic rings are fused to one another. Examples include1-naphthyl, 2-naphthyl, 1-anthracyl and 2-anthracyl. Also includedwithin the scope of the term “carbocyclic aromatic ring”, as it is usedherein, is a group in which an aromatic ring is fused to one or morenon-aromatic rings (carbocyclic or heterocyclic), such as in an indanyl,phthalimidyl, naphthimidyl, phenanthridinyl, or tetrahydronaphthyl,where the radical or point of attachment is on the aromatic ring.

The term “heteroaryl”, “heteroaromatic”, “heteroaryl ring”, “heteroarylgroup” and “heteroaromatic group”, used alone or as part of a largermoiety as in “heteroaralkyl” refers to heteroaromatic ring groups havingfive to fourteen members, including monocyclic heteroaromatic rings andpolycyclic aromatic rings in which a monocyclic aromatic ring is fusedto one or more other aromatic ring. Heteroaryl groups have one or morering heteroatoms. Examples of heteroaryl groups include 2-furanyl,3-furanyl, N-imidazolyl, 2-imidazolyl, 4-imidazolyl, 5-imidazolyl,3-isoxazolyl, 4-isoxazolyl, 5-isoxazolyl, 2-oxadiazolyl, 5-oxadiazolyl,2-oxazolyl, 4-oxazolyl, 5-oxazolyl, 3-pyrazolyl, 4-pyrazolyl,1-pyrrolyl, 2-pyrrolyl, 3-pyrrolyl, 2-pyridyl, 3-pyridyl, 4-pyridyl,2-pyrimidinyl, 4-pyrimidinyl, 5-pyrimidinyl, 3-pyridazinyl, 2-thiazolyl,4-thiazolyl, 5-thiazolyl, 2-triazolyl, 5-triazolyl, tetrazolyl,2-thienyl, 3-thienyl, carbazolyl, 2-benzothienyl, 3-benzothienyl,2-benzofuranyl, 3-benzofuranyl, 2-indolyl, 3-indolyl, 2-quinolinyl,3-quinolinyl, 2-benzothiazole, 2-benzooxazole, 2-benzimidazole,2-quinolinyl, 3-quinolinyl, 1-isoquinolinyl, 3-quinolinyl, 1-isoindolyland 3-isoindolyl. Also included within the scope of the term“heteroaryl”, as it is used herein, is a group in which an aromatic ringis fused to one or more non-aromatic rings (carbocyclic orheterocyclic), where the radical or point of attachment is on thearomatic ring.

The term “heteroatom” means nitrogen, oxygen, or sulfur and includes anyoxidized form of nitrogen and sulfur, and the quaternized form of anybasic nitrogen. Also the term “nitrogen” includes a substitutablenitrogen of a heteroaryl or non-aromatic heterocyclic group. As anexample, in a saturated or partially unsaturated ring having 0-3heteroatoms selected from oxygen, sulfur or nitrogen, the nitrogen maybe N (as in 3,4-dihydro-2H-pyrrolyl), NH (as in pyrrolidinyl) or NR″ (asin N-substituted pyrrolidinyl), wherein R″ is a suitable substituent forthe nitrogen atom in the ring of a non-aromatic nitrogen-containingheterocyclic group, as defined below.

An “aralkyl group”, as used herein is an alkyl groups substituted withan aryl group as defined above.

An optionally substituted aryl group as defined herein may contain oneor more substitutable ring atoms, such as carbon or nitrogen ring atoms.Examples of suitable substituents on a substitutable ring carbon atom ofan aryl group include —OH, C1-C3 alkyl, C1-C3 haloalkyl, —NO₂, C1-C3alkoxy, C1-C3 haloalkoxy, —CN, —NH₂, C1-C3 alkylamino, C1-C3dialkylamino, —C(O)NH₂, —C(O)NH(C1-C3 alkyl), —C(O)(C1-C3 alkyl),—NHC(O)H, —NHC(O)(C1-C3 alkyl), —C(O)N(C1-C3 alkyl)₂, —NHC(O)O—(C1-C3alkyl), —C(O)OH, —C(O)O—(C1-C3 alkyl), —NHC(O)NH₂, —NHC(O)NH(C1-C3alkyl), —NHC(O)N(C1-C3 alkyl)₂, —SO₂NH₂—SO₂NH(C1-C3alkyl),—SO₂N(C1-C3alkyl)₂, NHSO₂H or NHSO₂(C1-C3 alkyl). Preferred substituentson aryl groups are as defined throughout the specification. In certainembodiments optionally substituted aryl groups are unsubstituted.

Examples of suitable substituents on a substitutable ring nitrogen atomof an aryl group include C1-C3 alkyl, NH₂, C1-C3 alkylamino, C1-C3dialkylamino, —C(O)NH₂, —C(O)NH(C1-C3 alkyl), —C(O)(C1-C3 alkyl),—CO₂R**, —C(O)C(O)R**, —C(O)CH₃, —C(O)OH, —C(O)O—(C1-C3 alkyl),—SO₂NH₂—SO₂NH(C1-C3alkyl), —SO₂N(C1-C3alkyl)₂, NHSO₂H, NHSO₂(C1-C3alkyl), —C(═S)NH₂, —C(═S)NH(C1-C3 alkyl), —C(═S)N(C1-C3 alkyl)₂,—C(═NH)—N(H)₂, —C(═NH)—NH(C1-C3 alkyl) and —C(═NH)—N(C1-C3 alkyl)₂,

An optionally substituted alkyl group as defined herein may contain oneor more substituents. Examples of suitable substituents for an alkylgroup include those listed above for a substitutable carbon of an aryland the following: ═O, ═S, ═NNHR**, ═NN(R**)₂, ═NNHC(O)R**, ═NNHCO₂(alkyl), ═NNHSO₂ (alkyl), ═NR**, Spiro cycloalkyl group or fusedcycloalkyl group. R** in each occurrence, independently is —H or C1-C6alkyl. Preferred substituents on alkyl groups are as defined throughoutthe specification. In certain embodiments optionally substituted alkylgroups are unsubstituted.

A “Spiro cycloalkyl” group is a cycloalkyl group which shares one ringcarbon atom with a carbon atom in an alkylene group or alkyl group,wherein the carbon atom being shared in the alkyl group is not aterminal carbon atom.

Without wishing to be bound by any theory or limited to any mechanism itis believed that macromolecular antioxidants of the present inventionexploit the differences in activities (ks, equilibrium constant) of, forexample, homo- or hetero-type antioxidant moieties. Antioxidant moietiesinclude, for example, hindered phenolic groups, unhindered phenolicgroups, aminic groups and thioester groups, etc. of which there can beone or more present in each macromolecular antioxidant molecule. As usedherein a homo-type antioxidant macromolecule comprises antioxidantmoieties which are all same, for example, hindered phenolic, —OH groups.As used herein a hetero-type antioxidant macromolecule comprises atleast one different type of moiety, for example, hindred phenolic andaminic groups in the one macromolecule.

This difference in activities can be the result of, for example, thesubstitutions on neighboring carbons or the local chemical or physicalenvironment (for example, due to electrochemical or stereochemicalfactors) which can be due in part to the macromolecular nature ofmolecules.

In one embodiment of the present invention, a series of macromolecularantioxidant moieties of the present invention with different chemicalstructures can be represented by W1H, W2H, W3H, . . . to WnH. In oneembodiment of the present invention, two types of antioxidant moietiesof the present invention can be represented by: W1H and W2H. In certainembodiments W1H and W2H can have rate constants of k1 and k2respectively. The reactions involving these moieties and peroxylradicals can be represented as:

$\begin{matrix}{{{{ROO}.{+ W}}\; 1H}\overset{k\; 1}{\rightarrow}{{ROOH} + {W\; 1.}}} & (1) \\{{{{ROO}.{+ W}}\; 2H}\overset{k\; 2}{\rightarrow}{{ROOH} + {W\; 2.}}} & (2)\end{matrix}$where ROO. is a peroxyl radical resulting from, for example, initiationsteps involving oxidation activity, for example:RH→R.+H.  (3)R.+O2→ROO.  (4)

In one particular embodiment of the present invention k1>>k2 inequations (1) and (2). As a result, the reactions would take place insuch a way that there is a decrease in concentration of W1. freeradicals due their participation in the regeneration of active moietyW2H in the molecule according equation (5):W1.+W2H→W1H+W2.  (5) (transfer equilibrium)

This transfer mechanism may take place either in intra- orinter-molecular macromolecules. The transfer mechanism (5) could takeplace between moieties residing on the same macromolecule (intra-type)or residing on different macromolecules (inter-type).

In certain embodiments of the present invention, the antioxidantproperties described immediately above (equation 5) of themacromolecular antioxidants of the present invention result inadvantages including, but not limited to:

-   -   a) Consumption of free radicals W1. according to equation (5)        can result in a decrease of reactions of W1. with hydroperoxides        and hydrocarbons (RH).    -   b) The regeneration of W1H provides extended protection of        materials. This is a generous benefit to sacrificial type of        antioxidants that are used today. Regeneration of W1H assists in        combating the oxidation process The increase in the        concentration of antioxidant moieties W1H (according to        equation 5) extends the shelf life of materials.

In certain embodiments of the present invention, the following items areof significant interest for enhanced antioxidant activity in the designof the macromolecular antioxidants of the present invention:

-   -   a) The activity of proposed macromolecular antioxidant is        dependent on the regeneration of W1H in equation (5) either        through inter- or intra-molecular activities involving homo- or        hetero-type antioxidant moieties.    -   b) Depending on the rates constants of W1H and W2H it is        possible to achieve performance enhancements by many multiples        and not just incremental improvements.

In certain embodiments of the present invention, more than two types ofantioxidant moieties with different rate constants are used in themethods of the present invention.

In certain embodiments, the present invention pertains to the use of thedisclosed compounds to inhibit oxidation in an oxidizable material.

For purposes of the present invention, a method of “inhibitingoxidation” is a method that inhibits the propagation of a freeradical-mediated process. Free radicals can be generated by heat, light,ionizing radiation, metal ions and some proteins and enzymes. Inhibitingoxidation also includes inhibiting reactions caused by the presence ofoxygen, ozone or another compound capable of generating these gases orreactive equivalents of these gases.

As used herein the term “oxidizable material” is any material which issubject to oxidation by free-radicals or oxidative reaction caused bythe presence of oxygen, ozone or another compound capable of generatingthese gases or reactive equivalents thereof.

Antioxidant compounds of the present invention can be used to preventoxidation in a wide variety of compositions where free radical mediatedoxidation leads to deterioration of the quality of the composition,including edible products such as oils, foods (e.g., meat products,dairy products, cereals, etc.), and other products containing fats orother compounds subject to oxidation. Antioxidant compounds can also bepresent in plastics and other polymers, elastomers (e.g., natural orsynthetic rubber), petroleum products (e.g., fossil fuels such asgasoline, kerosene, diesel oil, heating oil, propane, jet fuel),lubricants, paints, pigments or other colored items, soaps and cosmetics(e.g., creams, lotions, hair products). The antioxidant compounds can beused to coat a metal as a rust and corrosion inhibitor. Antioxidantcompounds additionally can protect antioxidant vitamins (Vitamin A,Vitamin C, Vitamin E) and pharmaceutical products from degradation. Infood products, the antioxidant compounds can prevent rancidity. Inplastics, the antioxidant compounds can prevent the plastic frombecoming brittle and cracking.

Antioxidant compounds of the present invention can be added to oils toprolong their shelf life and properties. These oils can be formulated asvegetable shortening or margarine. Oils generally come from plantsources and include cottonseed oil, linseed oil, olive oil, palm oil,corn oil, peanut oil, soybean oil, castor oil, coconut oil, saffloweroil, sunflower oil, canola (rapeseed) oil and sesame oil. These oilscontain one or more unsaturated fatty acids such as caproleic acid,palmitoleic acid, oleic acid, vaccenic acid, elaidic acid, brassidicacid, erucic acid, nervonic acid, linoleic acid, eleosteric acid,alpha-linolenic acid, gamma-linolenic acid, and arachidonic acid, orpartially hydrogenated or trans-hydrogenated variants thereof.Antioxidant compounds of the present invention are also advantageouslyadded to food or other consumable products containing one or more ofthese fatty acids.

The shelf life of many materials and substances contained within thematerials, such as packaging materials, are enhanced by the presence ofan antioxidant compound of the present invention. The addition of anantioxidant compound to a packaging material is believed to provideadditional protection to the product contained inside the package. Inaddition, the properties of many packaging materials themselves,particularly polymers, are enhanced by the presence of an antioxidantregardless of the application (i.e., not limited to use in packaging).Common examples of packaging materials include paper, cardboard andvarious plastics and polymers. A packaging material can be coated withan antioxidant compound (e.g., by spraying the antioxidant compound orby applying as a thin film coating), blended with or mixed with anantioxidant compound, or otherwise have an antioxidant compound presentwithin it.

The entire teachings of each of the following applications areincorporated herein by reference:

-   Provisional Patent Application No. 60/632,893, filed Dec. 3, 2004,    Title: Process For The Synthesis Of Polyalkylphenol Antioxidants, by    Suizhou Yang, et al;-   Provisional Patent Application No. 60/633,197, filed Dec. 3, 2004,    Title: Synthesis Of Sterically Hindered Phenol Based Macromolecular    Antioxidants, by Ashish Dhawan, et al.;-   Provisional Patent Application No. 60/633,252, filed Dec. 3, 2004,    Title: One Pot Process For Making Polymeric Antioxidants, by    Vijayendra Kumar, et al.;-   Provisional Patent Application No. 60/633,196, filed Dec. 3, 2004,    Title: Synthesis Of Aniline And Phenol-Based Macromonomers And    Corresponding Polymers, by Rajesh Kumar, et al.;-   Patent application Ser. No. 11/184,724, filed Jul. 19, 2005 (U.S.    Patent Publication No. 2006/0041094 published Feb. 23, 2006), Title:    Anti-Oxidant Macromonomers And Polymers And Methods Of Making And    Using The Same, by Ashok L. Cholli;-   Patent application Ser. No. 11/184,716 filed Jul. 19, 2005 (U.S.    Patent Publication No. 2006/0041087 published Feb. 23, 2006), Title:    Anti-Oxidant Macromonomers And Polymers And Methods Of Making And    Using The Same, by Ashok L. Cholli;-   Provisional Patent Application No. 60/655,169, filed Feb. 22, 2005,    Title: Nitrogen And Hindered Phenol Containing Dual Functional    Macromolecules: Synthesis And Their Antioxidant Performances In    Organic Materials, by Rajesh Kumar, et al.-   Provisional Patent Application No. 60/655,169, filed Mar. 25, 2005,    Title: Alkylated Macromolecular Antioxidants And Methods Of Making,    And Using The Same, by Rajesh Kumar, et al.-   Provisional Patent Application No. 60/731,125, filed Oct. 27, 2005,    Title: Macromolecular Antioxidants And Polymeric Macromolecular    Antioxidants, by Ashok L. Cholli, et al.-   Patent application Ser. No. 11/040,193, filed Jan. 21, 2005 (U.S.    Pat. No. 7,323,511 issued Jan. 29, 2008), Title: Post-Coupling    Synthetic Approach For Polymeric Antioxidants, by Ashok L. Choll, et    al.;-   Patent Application No. PCT/US2005/001948, filed Jan. 21, 2005 (WO    2005/070974 published Aug. 4, 2005), Title: Post-Coupling Synthetic    Approach For Polymeric Antioxidants, by Ashok L. Cholli et al.;-   Patent Application No. PCT/US2005/001946, filed Jan. 21, 2005 (WO    2005/071005 published Aug. 4, 2005), Title: Polymeric Antioxidants,    by Ashok L. Choll, et al.;-   Patent Application No. PCT/US03/10782, filed Apr. 4, 2003 (WO    2003/087260 published Oct. 23, 2003), Title: Polymeric Antioxidants,    by Ashok L. Choll, et al.;-   Patent application Ser. No. 10/761,933, filed Jan. 21, 2004 (U.S.    Pat. No. 7,595,074 issued Sep. 29, 2009), Title: Polymeric    Antioxidants, by Ashish Dhawan, et al.;-   Patent application Ser. No. 10/408,679, filed Apr. 4, 2003 (U.S.    Pat. No. 7,223,432 issued May 29, 2007), Title: Polymeric    Antioxidants, by Ashok L. Choll, et al.;

In another particular embodiment, the present invention relates to aprocess for preparing compounds of the present invention. Compounds ofthe present invention can be prepared by a one pot process, comprisingthe step of combining a phenol containing compound with a suitablephosphorous containing compound in a suitable solvent under conditionssuitable for the reaction of the phenol containing compound with thephosphorous containing compound.

Suitable phenol containing compounds include:

where the vales and preferred values for the variables are as describedabove.

Suitable phosphorous containing compounds are those which are capable ofreacting with phenol containing compounds to produce compoundsrepresented by Structural Formula I-III, including, for example,phosphorous trichloride, phosphorous pentachloride, phosphoric acid andphosphoryl trichloride.

Suitable solvents are those which do not contain any acidic protons anddissolve the starting material and the side products, but do notdissolve the end product. Examples of suitable solvents include, forexample, dichloromethane, toluene, tetrahydrofuran, dichloromethane,chloroform, dioxane and acetonitrile.

In certain embodiments, the reaction of the phenol containing compoundwith the phosphorous containing compound occurs at 25° C. In otherembodiments, the reaction of the phenol containing compound with thephosphorous containing compound occurs below 25° C. In otherembodiments, the reaction of the phenol containing compound with thephosphorous containing compound occurs at a temperature between 25° C.and 0° C. In other embodiments, the reaction of the phenol containingcompound with the phosphorous containing compound occurs at atemperature between 15° C. and 0° C. In other embodiments, the reactionof the phenol containing compound with the phosphorous containingcompound occurs at a temperature between 5° C. and 0° C. In otherembodiments, the reaction of the phenol containing compound with thephosphorous containing compound occurs at 0° C.

In certain embodiment, the reaction of the phenol containing compoundwith the phosphorous containing compound takes place under a nitrogenatmosphere.

In certain embodiments the reaction takes place over 5 hours. In certainother embodiment the reaction takes place in less than 5 hours. Incertain other embodiments the reaction takes place in one hour. Incertain other embodiment the reaction takes place in less than one hour.In certain other embodiments the reaction takes place for a period of 30to 40 minutes.

In certain embodiment after completion of the reaction the suitablesolvent is removed by distillation

In certain other embodiments after the suitable solvent is distilledoff, the compound of the present invention are purified viacrystallization using techniques known in the art.

In certain embodiments, after crystallization, the crystals are furtherfiltered and washed using techniques known in the art.

Scheme 1 is a representative example of the synthesis of a compound ofthe present invention.

Scheme 1, shows the synthesis of a sterically hindered phenol andphosphite based compound of structural formula I.

The macromolecular antioxidant S was synthesized by one pot reaction ofphenol with phosphorous trichloride using dichloromethane as a solventat 0° C. The yield of the title compound was more than 95%.

Scheme 2, shows the synthesis of a sterically hindered phenol andphosphite based compound of structural formula II.

Scheme 3, shows the synthesis of a sterically hindered phenol andphosphite based compound of structural formula III.

The following is an example of one embodiment of the invention and isnot to be considered limiting in any way.

In one embodiment the sterically hindered phenol and phosphate basedantioxidant is:

EXEMPLIFICATION Example 1 Preparation oftris[N-(4-hydroxyphenyl),-3-(2,6-di-tert.-butyl,4-hydroxyphenyl)propionamide]phosphite, S

A 1 L two-necked round bottom flask equipped with a thermometer, adropping funnel and a nitrogen inlet was charged with 100 g (0.271 mole)of N-(4-hydroxyphenyl)-3-(2,6-di-tert-butyl, 4-hydroxyphenyl)propionamide, 22 ml (0.271 mole) pyridine in 200 ml ofdichloromethane. 7.86 ml (9.033 mmol) of phosphorous trichloride wasthen added dropwise at a temperature of 0 to 5° C. under nitrogenatmosphere for a period of 30 to 40 minutes. After the addition, thefunnel was removed and completion of the reaction was checked byTLC/HPLC. After completion, the dichloromethane was distilled out at 40°C. To the residue was added 100 ml of methanol to get white crystallineprecipitate, which was then filtered and washed several times with coldmethanol. The product was characterized by spectroscopic techniques. Themelting point is in the range of 224-245° C.

Example 2 Stabilization of polypropylene bytris[N-(4-hydroxyphenyl),-3-(2,6-di-tert.-butyl, 4-hydroxyphenyl)propionamide]phosphite S

1000 ppm of S was added to unstabilized polypropylene powder andextruded with single screw extruder in the form wires which was thenpalletized using a pelletizer. The pelltized sample of polypropylene wassubjected to an accelerated oxidative stability test using differentialscanning calorimetry (DSC) (ASTM D3895 method).

The results are shown in FIG. 1, which shows thattris[N-(4-hydroxyphenyl),-3-(2,6-di-tert.-butyl,4-hydroxyphenyl)propionamide]phosphite has a significantly higheroxidative induction time than commercially available Irganox®1010 inpolypropylene (PP) at 1000 ppm (extruded at 230° C.). For IRGANOX 1010,the onset Y value is 21.9526 mW and the onset X value is 11.206 minutes.For tris[N-(4-hydroxyphenyl),-3-(2,6-di-tert.-butyl,4-hydroxyphenyl)propionamide]phosphate, the onset Y value is 23.0327 mW,and the onset X value is 36.221 minutes.

While this invention has been particularly shown and described withreferences to preferred embodiments thereof, it will be understood bythose skilled in the art that various changes in form and details may bemade therein without departing from the scope of the inventionencompassed by the appended claims.

What is claimed is:
 1. A method of synthesizing a macromonomerrepresented by the following structural formula:

comprising the step of mixing

pyridine, and PCl₃ in a solvent under conditions that cause at leastpartial formation of the macromonomer.
 2. The method of claim 1, whereinthe solvent includes THF.
 3. The method of claim 1, wherein the solventincludes dichloromethane.
 4. The method of claim 1, wherein the mixingoccurs at a temperature in a range of between about 5° C. and about −5°C.
 5. The method of claim 1, wherein the mixing occurs at a temperatureof about 0° C.